| 名稱 | SN-38 |
| 描述 | SN-38 (NK012) is the active metabolite of Irinotecan, a DNA topoisomerase I (Topo I) inhibitor, which inhibits DNA and RNA synthesis (IC50=0.077/1.3 μM). SN-38 has antitumor activity and induces autophagy. |
| 細胞實驗 | MTT assay(Only for Reference) |
| 激酶實驗 | Topoisomerase I Assay: One unit (the minimum amount for full relaxation of 0.5 μg SV40 DNA under the conditions of this study) of topoisomerase I, 0.5 μL of the test compounds, and 0.5μg SV40 DNA are added sequentially to the reaction buffer, which is composed of 25 mM Tris-HCl (pH 7.5), 50 mM KC1, 5 mM MgCl2, 0.25 mM EDTA disodium salt, 0.25 mM dithiothreitol, 15μg /mL bovine serum albumin, and 5% glycerol. Then, the reaction mixture (50 μL) is incubated for 10 min at 37 °C, and the reaction is terminated by treatment with 7.5 μL of a solution consisting of 1% sodium dodecyl sulfate, 20 mM EDTA disodium salt, and 0.5 mg/mL proteinase K for an additional 30 min at 37°C. The samples are mixed with 5 μL of the loading buffer containing 10 mM Na2HPO4, 31.3% sucrose, and 0.3% bromophenol blue. Relaxed (form Ir) DNA is separated from supercoiled (form I) and nicked (form II) DNA by electrophoresis on 0.8% agarose gel at 50 mA and 20 V for 17 h in the presence of 2 μg/mL chloroquine, 10 mM EDTA, 30 mM NaH2PO4, and 36 Mm Tris-HCl (pH 7.8). After electrophoresis, the gel is stained with 0.05% ethidium bromide and photographed with UV light (302 nm). The amount of DNA is quantified using a densitometer. |
| 體外活性 | 方法：肺癌細胞 LLC、A549 和 H358 用 SN-38 (10-1000 nM) 處理 48 h，使用 MTT assay 檢測細胞活力。
結(jié)果：SN-38 在 10 nM 濃度下開始表現(xiàn)出作用，并在 100 nM 下誘導(dǎo)約 50% 的細胞死亡。[1]
方法：結(jié)直腸癌細胞 KM12C、KM12SM 和 KM12L4a 用 SN-38 (2.5 μg/mL) 處理 4-48 h，使用 Flow cytometry 檢測細胞周期和凋亡。
結(jié)果：SN-38 誘導(dǎo)的 S 期和 G2 期阻滯，KM12L4a 細胞以時間依賴性反應(yīng)最強。KM12SM 和 KM12L4a 細胞系的凋亡率隨時間增加，但在 KM12C 細胞中沒有這種變化。[2] |
| 體內(nèi)活性 | 方法：為檢測體內(nèi)抗腫瘤活性，將 SN-38 (2 mg/kg) 單次腹腔注射給腹膜腔內(nèi)移植 LLC 細胞的 C57BL/6 小鼠。
結(jié)果：單次腹腔注射 SN-38 可顯著減弱 LLC 腫瘤的生長，使腫瘤生長減少 22.7%。[1]
方法：為檢測體內(nèi)抗腫瘤活性，將 SN-38 (10 mg/kg in 0.5% carboxymethylcellulose sodium，腹腔注射) 和 gefitinib (100 mg/kg，皮下注射) 攜帶人口腔鱗狀腫瘤 HSC-2 的 BALB/c nude 小鼠，每周五次，持續(xù)三周。
結(jié)果：僅 gefitinib 治療和 gefitinib 加 SN-38 治療在腫瘤生長抑制方面沒有顯著差異。然而，當(dāng)治療停止后繼續(xù)進行腫瘤測量時，僅吉非替尼組的一些腫瘤顯示出新的生長。[3] |
| 存儲條件 | store at low temperature | Powder: -20°C for 3 years | In solvent: -80°C for 1 year | Shipping with blue ice. |
| 溶解度 | 10% DMSO+40% PEG300+5% Tween 80+45% Saline : 3.92 mg/mL (9.99 mM), Suspension. Please add co-solvents sequentially, clarifying the solution as much as possible before adding the next one. Dissolve by heating and/or sonication if necessary. Working solution is recommended to be prepared and used immediately.
DMSO : 50 mg/mL (127.4 mM), Sonication is recommended.
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| 關(guān)鍵字 | Topoisomerase | inhibit | NK 012 | Inhibitor | ADC Cytotoxin | SN38 | SN-38 | ADC Payload | NK-012 | Autophagy |
| 相關(guān)產(chǎn)品 | Guanidine hydrochloride | Naringin | Taurine | Gefitinib | Hydroxychloroquine | Stavudine | Thymidine | Paeonol | Sodium 4-phenylbutyrate |
| 相關(guān)庫 | 抗癌活性化合物庫 | 已知活性化合物庫 | 生物堿類天然產(chǎn)物庫 | 抗癌天然產(chǎn)物庫 | 抗衰老化合物庫 | 天然產(chǎn)物庫 | 藥物功能重定位化合物庫 | 高通量篩選天然產(chǎn)物庫 | 抗癌臨床化合物庫 | 抗癌藥物庫 |